Nature Genetics
34, 181 - 186 (2003)
Published online: 18 May 2003; | doi:10.1038/ng1166
Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthmaYouming Zhang1, Nicholas I Leaves1, 6, Gavin G Anderson1, 6, Chris P Ponting2, John Broxholme1, Richard Holt1, Pauline Edser1, Sumit Bhattacharyya1, Andy Dunham3, Ian M Adcock4, Louise Pulleyn4, Peter J Barnes4, John I Harper5, Gonçalo Abecasis1, Lon Cardon1, Melanie White1, John Burton3, Lucy Matthews3, Richard Mott1, Mark Ross3, Roger Cox1, Miriam F Moffatt1
& William O C M Cookson11
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. 2
Medical Research Council Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, UK. 3
Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. 4
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK. 5
Great Ormond Street Hospital and the Institute for Child Health, London, UK. 6
These authors contributed equally to this work.
Correspondence should be addressed to William O C M Cookson william.cookson@ndm.ox.ac.ukAtopic or immunoglobulin E (IgE)-mediated diseases include the common disorders of asthma, atopic dermatitis and allergic rhinitis1. Chromosome 13q14 shows consistent linkage to atopy and the total serum IgE concentration2,
3,
4,
5,
6. We previously identified association between total serum IgE levels and a novel 13q14 microsatellite (USAT24G1; ref. 7) and have now localized the underlying quantitative-trait locus (QTL) in a comprehensive single-nucleotide polymorphism (SNP) map. We found replicated association to IgE levels that was attributed to several alleles in a single gene, PHF11. We also found association with these variants to severe clinical asthma. The gene product (PHF11) contains two PHD zinc fingers and probably regulates transcription. Distinctive splice variants were expressed in immune tissues and cells.
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